Under conditions of chronic pulmonary ischemia, the bronchial circulation undergoes massive proliferation. The functional consequences of this rapidly constructed circulation remain largely unexplored. Systemic angiogenic beds outside the lung parenchyma generally demonstrate a proinflammatory phenotype. Whether a proinflammatory bronchial lung neovasculature contributes to interstitial edema, inflammation, and decrements in pulmonary function is unknown. Our laboratory has studied systemic angiogenesis in mice after chronic left pulmonary artery ligation (LPAL) where inflammatory cytokines, predominantly ELR+ CXC chemokines, appear to play a role in intercostal artery angiogenesis. However, as mice lack an intraparenchymal bronchial circulation, a larger animal model with a bronchial vascular anatomy similar to humans is required to determine the physiology of the angiogenic bronchial vasculature. We propose to study the process and consequences of bronchial vascular growth and proliferation after LPAL in rats. An underlying question in this model is how growth factors released within the perfusion- starved lung parenchyma communicate with distant, upstream bronchial vessels. We propose a conduit role for lung lymphatic vessels, which drain unidirectionally and in proximity to major bronchial arteries. We hypothesize that bronchial angiogenesis is dependent on growth factors (CXC chemokines) released by trapped inflammatory cells, that drain through lung lymphatics and mediastinal lymph nodes, causing bronchial vascular proliferation and enlargement. Furthermore, we hypothesize that the neovasculature is proinflammatory (vasodilated, hyperpermeable, leukocyte recruiting) and contributes to interstitial edema. We propose the following specific aims in a rat model of LPAL: Specific Aim 1: To determine the importance of proangiogenic ELR+ CXC chemokines for the growth of new bronchial blood vessels during chronic left pulmonary artery obstruction. Specific Aim 2: To determine whether mediastinal lymph drainage provides a mechanism whereby parenchymal growth factors transit upstream to promote angiogenesis of larger bronchial arteries. Specific Aim 3: To determine the physiologic function of the new bronchial vasculature and whether it exacerbates lung pathologic indices. We will measure bronchial vascular permeability and its affect on lung compliance and resistance at time points before and after the new vasculature is established. Pathologic angiogenesis of the bronchial circulation occurs during conditions of chronic inflammation such as cystic fibrosis, asthma, pulmonary fibrosis, lung cancer, and chronic thromboembolic disease. Thus, gaining knowledge of this process and its' consequences is highly relevant. [unreadable] [unreadable] [unreadable] [unreadable]